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Genetic architecture distinguishes systemic juvenile idiopathic arthritis from other forms of juvenile idiopathic arthritis: Clinical and therapeutic implications
Annals of the Rheumatic Diseases
  • Michael J. Ombrello, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
  • Victoria L. Arthur, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
  • Elaine F. Remmers, National Human Genome Research Institute (NHGRI)
  • Anne Hinks, Health Innovation Manchester
  • Ioanna Tachmazidou, Wellcome Sanger Institute
  • Alexei A. Grom, University of Cincinnati College of Medicine
  • Dirk Foell, Universitätsklinikum Münster
  • Alberto Martini, Università degli Studi di Genova
  • Marco Gattorno, Istituto Giannina Gaslini
  • Seza Özen, Hacettepe Üniversitesi
  • Sampath Prahalad, Emory University School of Medicine
  • Andrew S. Zeft, Cleveland Clinic Foundation
  • John F. Bohnsack, The University of Utah
  • Norman T. Ilowite, The Childen's Hospital at Montefiore
  • Elizabeth D. Mellins, Stanford University
  • Ricardo Russo, Fundacion Hospital de Pediatria Professor Dr. Juan P. Garrahan
  • Claudio Len, Universidade Federal de São Paulo
  • Maria Odete E. Hilario, Universidade Federal de São Paulo
  • Sheila Oliveira, Universidade Federal do Rio de Janeiro
  • Rae S.M. Yeung, University of Toronto
  • Alan M. Rosenberg, University of Saskatchewan, College of Medicine
  • Lucy R. Wedderburn, UCL Great Ormond Street Institute of Child Health
  • Jordi Anton, Universitat de Barcelona
  • Johannes Peter Haas, German Center for Pediatric and Adolescent Rheumatology
  • Angela Rosen-Wolff, Universitätsklinikum Carl Gustav Carus Dresden
  • Kirsten Minden, Charité – Universitätsmedizin Berlin
  • Klaus Tenbrock, Rheinisch-Westfälische Technische Hochschule Aachen
  • Erkan Demirkaya, Hacettepe Üniversitesi
  • Joanna Cobb, Health Innovation Manchester
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Objectives Juvenile idiopathic arthritis (JIA) is a heterogeneous group of conditions unified by the presence of chronic childhood arthritis without an identifiable cause. Systemic JIA (sJIA) is a rare form of JIA characterised by systemic inflammation. sJIA is distinguished from other forms of JIA by unique clinical features and treatment responses that are similar to autoinflammatory diseases. However, approximately half of children with sJIA develop destructive, long-standing arthritis that appears similar to other forms of JIA. Using genomic approaches, we sought to gain novel insights into the pathophysiology of sJIA and its relationship with other forms of JIA. Methods We performed a genome-wide association study of 770 children with sJIA collected in nine countries by the International Childhood Arthritis Genetics Consortium. Single nucleotide polymorphisms were tested for association with sJIA. Weighted genetic risk scores were used to compare the genetic architecture of sJIA with other JIA subtypes. Results The major histocompatibility complex locus and a locus on chromosome 1 each showed association with sJIA exceeding the threshold for genome-wide significance, while 23 other novel loci were suggestive of association with sJIA. Using a combination of genetic and statistical approaches, we found no evidence of shared genetic architecture between sJIA and other common JIA subtypes. Conclusions The lack of shared genetic risk factors between sJIA and other JIA subtypes supports the hypothesis that sJIA is a unique disease process and argues for a different classification framework. Research to improve sJIA therapy should target its unique genetics and specific pathophysiological pathways.

Citation Information
Michael J. Ombrello, Victoria L. Arthur, Elaine F. Remmers, Anne Hinks, et al.. "Genetic architecture distinguishes systemic juvenile idiopathic arthritis from other forms of juvenile idiopathic arthritis: Clinical and therapeutic implications" Annals of the Rheumatic Diseases Vol. 76 Iss. 5 (2017)
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